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Plasma Sphingomyelin as a Post-Treatment Monitoring Biomarker for Pathological Response in Locally Advanced Rectal
Pedro Brandão1,2,3,4, Lúcia Lacerda2,3,4,5, Marisa D Santos1,2,3,4
1Colorectal Unit, Department of Surgery, Hospital de Santo António, Unidade Local de Saúde de Santo António (ULSSA), Largo Professor Abel Salazar, 4099-001 Porto, Portugal.
Cancers
|July 15, 2026
Summary
Plasma sphingomyelin (SM) shows promise as a post-treatment biomarker for assessing pathological response in locally advanced rectal cancer (LARC). This finding aids organ-preservation strategies by improving treatment response evaluation.
Area of Science:
- Oncology
- Biomarker Discovery
- Rectal Cancer Research
Background:
- Organ-preservation in locally advanced rectal cancer (LARC) necessitates precise response assessment after neoadjuvant therapy.
- Current MRI techniques struggle to differentiate complete from near-complete pathological responses.
- Investigating plasma sphingolipid dynamics offers a novel approach to monitor treatment efficacy.
Purpose of the Study:
- To evaluate plasma sphingolipid dynamics as potential biomarkers for pathological response in LARC patients.
- To determine if sphingomyelin (SM) can accurately predict treatment response post-neoadjuvant therapy.
- To compare the efficacy of SM as a biomarker against serum carcinoembryonic antigen (CEA).
Main Methods:
- A cohort of 86 LARC patients was studied, with 58 undergoing neoadjuvant treatment and surgical resection.
- Plasma levels of sphingomyelin (SM), sphingosine-1-phosphate, and glucosylceramide were measured at baseline, post-chemoradiotherapy, and post-surgery.
- Receiver operating characteristic (ROC) analysis and mixed-effects models were used to assess biomarker performance and longitudinal changes.
Main Results:
- Plasma SM levels did not predict response at baseline but showed significant discrimination after treatment (M1 AUC=0.750, M2 AUC=0.786).
- SM levels correlated inversely with tumor regression grade (TRG) and outperformed serum CEA in predicting response (SM AUC=0.74 vs. CEA AUC=0.60).
- Good responders exhibited a +22.5% increase in SM from baseline to post-surgery, while poor responders showed an 8.4% decrease.
Conclusions:
- Plasma sphingomyelin (SM) emerges as a valuable post-treatment monitoring biomarker for pathological response in LARC.
- SM can aid in multimodal response assessment, supporting organ-preservation decision-making in LARC management.
- Further external validation of plasma SM as a biomarker in independent cohorts is recommended.
